During this period, the project team completed primary high-throughput screening, and hits were cherrypicked and retested to validate their activity. The most promising hits were identified and followed up with medicinal chemistry and several series of analogs were synthesized. Candidates with attractive activity profiles were pursued with medicinal chemistry to synthesize a series of new analogs, which were advanced for testing in a TSHR overexpressing cell line to determine beta-Arrestin 1 signaling.